Non-invasive assessment of oxidative stress in preterm infants.

Preterm newborns have an immature antioxidant defense system and are especially susceptible to oxidative stress. Resuscitation, mechanical ventilation, intermittent hypoxia and apneic episodes require frequently oxygen supplementation which leads to oxidative stress in preterm newborns. The consequences of oxidative damage are increased short and long-term morbidities, neurodevelopmental impairment and increased mortality. Oxidative stress biomarkers are determined in blood samples from preterm children during their stay in neonatal intensive care units especially for research purposes. However, there is a tendency towards reducing invasive and painful techniques in the NICU (Neonatal Intensive Care Unit) and avoiding excessive blood extractions procedures. In this paper, it has been described some studies that employed non-invasive samples to determine oxidative stress biomarkers form preterm infants in order to perform a close monitoring biomarker with a significant greater predictive value. Among these methods we describe a previously developed and validated high-performance liquid chromatography tandem mass spectrometry method that allow to accurately determine the most reliable biomarkers in biofluids, which are non-invasively and painlessly obtained.

Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

AIM: Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. METHODS: Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. RESULTS: Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). CONCLUSION: The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

N-terminal B-type natriuretic peptide urinary concentrations and retinopathy of prematurity.

BackgroundTo validate the findings of a single-center pilot study showing elevated urinary N-terminal B-type natriuretic peptide (NTproBNP) concentrations in preterm infants subsequently developing severe retinopathy of prematurity (ROP) in a multicenter setting across eight European and Middle East countries.MethodsProspective observational study in 967 preterm infants <30 weeks' gestational age assessing the capacity of urinary NTproBNP on days of life (DOLs) 14 and 28 to predict ROP requiring treatment.ResultsUrinary NTproBNP concentrations were markedly elevated in infants who developed ROP requiring treatment (n=94) compared with survivors without ROP treatment (n=837), at both time points (median (interquartile range) DOL14: 8,950 (1,925-23,783) vs. 3,083 (1,193-17,393) vs. 816 (290-3,078) pg/ml, P<0.001) and DOL28 (2,203 (611-4,063) vs. 1,671 (254-11,340) vs. 408 (162-1,126) pg/ml, P<0.001). C-statistic of NTproBNP for treated ROP or death was 0.731 (95% confidence interval 0.654-0.774) for DOL14 and 0.683 (0.622-0.745) for DOL28 (P<0.001). Threshold scores were calculated, potentially enabling around 20% of infants with low NTproBNP scores never to be screened with ophthalmoscopy.ConclusionThere is a strong association between early urinary NTproBNP and subsequent ROP development, which can be used to further refine subgroups of patients with high or low risk of severe ROP.

Frequency of retinopathy of prematurity in premature neonates with a birth weight below 1500 grams and a gestational age less than 32 weeks: a study from a tertiary care hospital in a lower-middle income country .

INTRODUCTION: Retinopathy of prematurity (ROP) is a treatable cause of blindness in neonates. In Pakistan, ROP is often not recognized early because screening and treatment programs are not yet in place in most neonatal units, even in tertiary care hospitals. It is hoped that this report will help inform medical professionals of the magnitude of the problem and help to design appropriate management strategies. OBJECTIVES: The aim was to determine the frequency of ROP in premature and very low birth weight (BW) neonates (BW<1500 g and gestational age (GA) <32 weeks). STUDY DESIGN: Cross-sectional study. STUDY SETTING: Neonatal intensive care unit (NICU) of a tertiary care hospital in Karachi, Pakistan. STUDY DURATION: From June 2009 to May 2010. SUBJECTS AND METHODS: Neonates with a Birth weight (BW) <1500 g and Gestational Age (GA) <32 weeks who were admitted to the NICU and received an eye examination, or were referred for a ROP eye examination as an outpatient, were included in the study. GA was estimated from intrauterine ultrasound findings. Neonates with major congenital malformations, syndromes or congenital cataracts or tumors of the eyes, and those that died before the eye examination or did not attend the out patients department for an eye examination, were excluded. The neonatal eye examination was performed by a trained ophthalmologist at 4 or 6 weeks of age. RESULTS: Out of 86 neonates, ROP was identified in nine neonates (10.5%) at the first eye examination. ROP was significantly associated with BW (P = 0.037), GA (P = 0.033), and chronological age (P<0.001). CONCLUSIONS: we identified ROP in 10.5% of neonates at first eye examination. Significant associations between ROP and a GA<32 weeks and a BW<1500 g were also observed.we also stress that serial follow-up of neonates at risk for ROP is important when making a final diagnosis.

Low urine vascular endothelial growth factor levels are associated with mechanical ventilation, bronchopulmonary dysplasia and retinopathy of prematurity.

BACKGROUND: Organ-specific vascular endothelial growth factor (VEGF) expression is decreased during the pathogenesis of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) several weeks before either disease can be diagnosed. Early measurement of organ-specific tissue VEGF levels might allow identification of infants at high risk for these diseases, but is not clinically feasible. Urine VEGF is easily measured and useful in early diagnosis of several diseases. OBJECTIVES: Our aims were to assess the correlation of urine VEGF levels measured in the first postnatal month with subsequent BPD or ROP diagnosis and to determine whether various infant characteristics influence urine VEGF levels. METHODS: 106 subjects born at <29 weeks' gestation and surviving to 36 weeks' postmenstrual age were selected from an existing database and biorepository. Urine VEGF and total protein were measured in 2-3 samples per subject. RESULTS: Urine VEGF/protein levels increased by 72% per week (p < 0.0001) during the first postnatal month. In multivariable analysis controlling for postnatal age, lower VEGF/protein was associated with higher levels of mechanical respiratory support (p = 0.006), male gender (p = 0.001) and early sepsis (p = 0.003) but not with fraction of inspired oxygen. Lower urine VEGF/protein and mechanical ventilation were each associated with BPD and ROP. In analyses adjusted for respiratory support, lower urine VEGF/protein and ROP remained associated but urine VEGF/protein and BPD did not. CONCLUSIONS: Low urine VEGF/protein levels in the first postnatal month are associated with mechanical ventilation, BPD, and ROP.

Urinary N-terminal B-type natriuretic peptide predicts severe retinopathy of prematurity.

OBJECTIVE: The goal of this study was to evaluate urinary N-terminal fragment of B-type natriuretic peptide concentrations, normalized to creatinine (UNBCR), to predict morbidities at discharge in preterm infants. METHODS: UNBCR were determined in urine collected on day of life (DOL) 2, 7, 14, and 28 in 136 preterm infants <1500 g birth weight, 22 of whom developed bronchopulmonary dysplasia (BPD), defined as oxygen supplementation at 36 weeks' gestational age) and 11 infants developed severe retinopathy (ROP), defined as stage 3 or stage ≥ 2 requiring surgery). RESULTS: UNBCR on DOL 7, 14, and 28 was elevated in infants who developed BPD or ROP compared with controls (P ≤ .001). On multiple regression analysis including birth weight and gestational age, ROP but not BPD remained independently associated with UNBCR on DOL 14 and 28. Areas under receiver operating characteristic curves for UNBCR on DOL 14 and 28 to predict ROP were 0.938 (0.027) and 0.954 (0.021), respectively. UNBCR DOL 14 and 28 thresholds exceeded by all infants with severe ROP (100% sensitivity, 100% negative predictive value) had a specificity of 66% and 85%, respectively. CONCLUSIONS: UNBCR might hold promise to reduce unnecessary eye examinations by timely and accurate identification of infants at risk of severe ROP.